Cargando…
Melatonin Attenuates Cisplatin-Induced Acute Kidney Injury through Dual Suppression of Apoptosis and Necroptosis
Melatonin is well known to modulate the sleep–wake cycle. Accumulating evidence suggests that melatonin also has favorable effects such as anti-oxidant and anti-inflammatory properties in numerous disease models. It has been reported that melatonin has therapeutic effects against cisplatin-induced a...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6784065/ https://www.ncbi.nlm.nih.gov/pubmed/31480317 http://dx.doi.org/10.3390/biology8030064 |
_version_ | 1783457667539271680 |
---|---|
author | Kim, Jong Woo Jo, Jungmin Kim, Jung-Yeon Choe, Misun Leem, Jaechan Park, Jae-Hyung |
author_facet | Kim, Jong Woo Jo, Jungmin Kim, Jung-Yeon Choe, Misun Leem, Jaechan Park, Jae-Hyung |
author_sort | Kim, Jong Woo |
collection | PubMed |
description | Melatonin is well known to modulate the sleep–wake cycle. Accumulating evidence suggests that melatonin also has favorable effects such as anti-oxidant and anti-inflammatory properties in numerous disease models. It has been reported that melatonin has therapeutic effects against cisplatin-induced acute kidney injury (AKI). However, mechanisms underlying the therapeutic action of melatonin on the renal side-effects of cisplatin therapy remain poorly understood. In this study, we showed that melatonin treatment significantly ameliorates cisplatin-induced acute renal failure and histopathological alterations. Increased expression of tubular injury markers was largely reduced by melatonin. Melatonin treatment inhibited caspase-3 activation and apoptotic cell death. Moreover, protein levels of key components of the molecular machinery for necroptosis were decreased by melatonin. Melatonin also attenuated nuclear factor-κB activation and suppressed expression of pro-inflammatory cytokines. Consistent with in vivo findings, melatonin dose-dependently decreased apoptosis and necroptosis in cisplatin-treated mouse renal tubular epithelial cells. Collectively, our findings suggest that melatonin ameliorates cisplatin-induced acute renal failure and structural damages through dual suppression of apoptosis and necroptosis. These results reveal a novel mechanism underlying the therapeutic effect of melatonin against cisplatin-induced AKI and strengthen the idea that melatonin might be a promising therapeutic agent for the renal side-effects of cisplatin therapy. |
format | Online Article Text |
id | pubmed-6784065 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-67840652019-10-16 Melatonin Attenuates Cisplatin-Induced Acute Kidney Injury through Dual Suppression of Apoptosis and Necroptosis Kim, Jong Woo Jo, Jungmin Kim, Jung-Yeon Choe, Misun Leem, Jaechan Park, Jae-Hyung Biology (Basel) Article Melatonin is well known to modulate the sleep–wake cycle. Accumulating evidence suggests that melatonin also has favorable effects such as anti-oxidant and anti-inflammatory properties in numerous disease models. It has been reported that melatonin has therapeutic effects against cisplatin-induced acute kidney injury (AKI). However, mechanisms underlying the therapeutic action of melatonin on the renal side-effects of cisplatin therapy remain poorly understood. In this study, we showed that melatonin treatment significantly ameliorates cisplatin-induced acute renal failure and histopathological alterations. Increased expression of tubular injury markers was largely reduced by melatonin. Melatonin treatment inhibited caspase-3 activation and apoptotic cell death. Moreover, protein levels of key components of the molecular machinery for necroptosis were decreased by melatonin. Melatonin also attenuated nuclear factor-κB activation and suppressed expression of pro-inflammatory cytokines. Consistent with in vivo findings, melatonin dose-dependently decreased apoptosis and necroptosis in cisplatin-treated mouse renal tubular epithelial cells. Collectively, our findings suggest that melatonin ameliorates cisplatin-induced acute renal failure and structural damages through dual suppression of apoptosis and necroptosis. These results reveal a novel mechanism underlying the therapeutic effect of melatonin against cisplatin-induced AKI and strengthen the idea that melatonin might be a promising therapeutic agent for the renal side-effects of cisplatin therapy. MDPI 2019-08-30 /pmc/articles/PMC6784065/ /pubmed/31480317 http://dx.doi.org/10.3390/biology8030064 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Kim, Jong Woo Jo, Jungmin Kim, Jung-Yeon Choe, Misun Leem, Jaechan Park, Jae-Hyung Melatonin Attenuates Cisplatin-Induced Acute Kidney Injury through Dual Suppression of Apoptosis and Necroptosis |
title | Melatonin Attenuates Cisplatin-Induced Acute Kidney Injury through Dual Suppression of Apoptosis and Necroptosis |
title_full | Melatonin Attenuates Cisplatin-Induced Acute Kidney Injury through Dual Suppression of Apoptosis and Necroptosis |
title_fullStr | Melatonin Attenuates Cisplatin-Induced Acute Kidney Injury through Dual Suppression of Apoptosis and Necroptosis |
title_full_unstemmed | Melatonin Attenuates Cisplatin-Induced Acute Kidney Injury through Dual Suppression of Apoptosis and Necroptosis |
title_short | Melatonin Attenuates Cisplatin-Induced Acute Kidney Injury through Dual Suppression of Apoptosis and Necroptosis |
title_sort | melatonin attenuates cisplatin-induced acute kidney injury through dual suppression of apoptosis and necroptosis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6784065/ https://www.ncbi.nlm.nih.gov/pubmed/31480317 http://dx.doi.org/10.3390/biology8030064 |
work_keys_str_mv | AT kimjongwoo melatoninattenuatescisplatininducedacutekidneyinjurythroughdualsuppressionofapoptosisandnecroptosis AT jojungmin melatoninattenuatescisplatininducedacutekidneyinjurythroughdualsuppressionofapoptosisandnecroptosis AT kimjungyeon melatoninattenuatescisplatininducedacutekidneyinjurythroughdualsuppressionofapoptosisandnecroptosis AT choemisun melatoninattenuatescisplatininducedacutekidneyinjurythroughdualsuppressionofapoptosisandnecroptosis AT leemjaechan melatoninattenuatescisplatininducedacutekidneyinjurythroughdualsuppressionofapoptosisandnecroptosis AT parkjaehyung melatoninattenuatescisplatininducedacutekidneyinjurythroughdualsuppressionofapoptosisandnecroptosis |